Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors
Francotte, Pierre; De Tullio, Pascal; Goffin, Ericet al.
2007 • In Journal of Medicinal Chemistry, 50 (13), p. 3153-3157
[en] A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration.
Disciplines :
Chemistry Pharmacy, pharmacology & toxicology
Author, co-author :
Francotte, Pierre ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Université de Liège - ULiège > Chimie pharmaceutique
De Tullio, Pascal ; Université de Liège - ULiège > Chimie pharmaceutique
Goffin, Eric ; Université de Liège - ULiège > Chimie pharmaceutique
Fraikin, Pierre ; Université de Liège - ULiège > Chimie pharmaceutique
Lestage, Pierre
Danober, Laurence
Thomas, Jean-Yves
Caignard, Daniel-Henri
Pirotte, Bernard ; Université de Liège - ULiège > Chimie pharmaceutique
Language :
English
Title :
Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors
Publication date :
2007
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
Amer Chemical Soc, Washington, United States - Washington
Graindorge, E.; Francotte, P.; Boverie, S.; de Tullio, P.; Pirotte, B. New Trends in the Development of Positive Allosteric Modulators of AMPA Receptors. Curr. Med. Chem. 2004, 4, 95-103.
Hashimoto, K.; Okamura, N.; Shimizu, E.; Iyo, M. Glutamate Hypothesis of Schizophrenia and Approach for Possible Therapeutic Drugs. Curr. Med. Chem. 2004, 4, 147-154.
Lynch, G. AMPA Receptor Modulators as Cognitive Enhancers. Curr. Opin. Pharmacol. 2004, 4, 4-11.
Black, M. D. Therapeutic Potential of Positive AMPA Modulators and their Relationship to AMPA Receptor Subunits. A Review of Preclinical Data. Psychopharmacology 2005, 179, 154-163.
Francotte, P.; de Tullio, P.; Fraikin, P.; Counerotte, S.; Coffin, E.; Pirotte, B. In search of novel AMPA potentiators. Recent Pat. CNS Drug Discovery, 2006, 1, 239-246.
Yamada, K. A.; Tang, C. M. Benzothiadiazides Inhibit Rapid Glutamate Receptor Desensitization and Enhance Glutamatergic Synaptic Currents. J. Neurosci. 1993, 13, 3904-3915.
Lestage, P.; Danober, L.; Lockhart, B.; Roger, A.; Lebrun, C.; Robin, J.-L.; Desos, P.; Cordi, A. S 18986, Positive Allosteric Modulator of AMPA Receptors as a Novel Cognition Enhancer in Rodents. Res. Pract. Alzheimer's Dis. 2002, 6, 253-259.
Phillips, D.; Sonnenberg, J.; Arai, A. C.; Vaswani, R.; Krutzik, P. O.; Kleisli, T.; Kessler, M.; Granger, R.; Lynch, G.; Chamberlin, A. R. 5′-Alkyl-benzothiadiazides: A New Subgroup of AMPA Receptor Modulators with Improved Affinity. Bioorg. Med. Chem. 2002, 10, 1229-1248.
Braghiroli, D.; Puia, G.; Cannazza, G.; Tait, A.; Parenti, C.; Losi, G.; Baraldi, M. Synthesis of 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1 -Dioxide Derivatives as Potential Allosteric Modulators of AMPA/ Kainate Receptors. J. Med. Chem. 2002, 45, 2355-2357.
Pirotte, B.; Podona, T.; Diouf, O.; de Tullio, P.; Lebrun, P.; Dupont, L.; Somers, F.; Delarge, J.; Morain, P.; Lestage, P.; Lepagnol, J.; Spedding, M. 4H-1,2,4-Pyridothiadiazine 1,1-Dioxides and 2,3-Dihydro-4H-1,2,4- pyridothiadiazine 1,1-Dioxides Chemically Related to Diazoxide and Cyclothiazide as Powerful Positive Allosteric Modulators of (R/S)-2-Amino-3-(3- hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors: Design, Synthesis, Pharmacology, and Structure-Activity Relationships. J. Med. Chem. 1998, 41, 2946-2959.
Abramovitch, R. A.; Chellathurai, T.; Holcomb, W. D.; McMaster, I. T.; Vanderpool, D. P. Intramolecular Insertion of Arylsulfonylnitrenes into Aliphatic Side Chains. J. Org. Chem. 1977, 42, 2920-2926.
Hypotensive Sulfonamides, French Patent FR1381634, December 14, 1964.
Gruart, A.; Munoz, M. D.; Delgado-Garcia, J. M. Involvement of the CA3-CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice. J. Neurosci. 2006, 26, 1077-1087.
Lin, B.; Colgin, L. L.; Brucher, F. A.; Arai, A. C.; Lynch, G. Interactions between Recording Technique and AMPA Receptor Modulators. Brain Res. 2002, 955, 164-173.
Pittaluga, A.; Bonfanti, A.; Raiteri, M. Differential Desensitization of Ionotropic Non-NMDA Receptors Having Distinct Neuronal Location and Function. Naunyn-Schmiedeberg's Arch. Pharmacol. 1997, 356, 29-38.
Desai, M. A.; Burnett, J. P.; Schoepp, D. D. Cyclothiazide Selectively Potentiates AMPA- and Kainate-Induced [3H]Norepinephrine Release from Rat Hippocampal Slices. J. Neurochem. 1994, 63, 231-217.
Cowen, M. S.; Beart, P. M. Cyclothiazide and AMPA Receptor Desensitization: Analyses from Studies of AMPA-Induced Release of [ 3H]-Noradrenaline from Hippocampal Slices. Br. J. Pharmacol. 1998, 123, 473-480.
Lockhart, B.; Iop, F.; Closier, M.; Lestage, P. (S)-2,3-Dihydro- [3,4]-cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide: (S18986-1) A Positive Modulator of AMPA Receptors Enhances (S)-AMPA-mediated [ 3H]Noradrenaline Release from Rat Hippocampal and Frontal Cortex Slices. Eur. J. Pharmacol. 2000, 401, 145-153.
Ennaceur, A.; Delacour, J. A New One-Trial Test for Neurobiological Studies of Memory in Rats. 1: Behavioral Data. Behav. Brain Res. 1988, 31, 47-59.
Scali, C.; Casamenti, F.; Pazzagli, M.; Bartolini, L.; Pepeu, G. Nerve Growth Factor Increases Extracellular Acetylcholine Levels in the Parietal Cortex and Hippocampus of Aged Rats and Restores Object Recognition. Neurosci. Lett. 1994, 170, 117-120.
Bartolini, L.; Casamenti, F.; Pepeu, G. Aniracetam Restores Object Recognition Impaired by Age, Scopolamine, and Nucleus Basalis Lesions. Pharmacol. Biochem. Behav. 1996, 53, 277-283.
Lebrun, C.; Pilliere, E.; Lestage, P. Effects of S 18986-1, A Novel Cognitive Enhancer, on Memory Performances in an Object Recognition task in Rats. Eur. J. Pharmacol. 2000, 401, 205-212.
